Emerging Therapies for the Treatment of Psoriasis

Psoriasis is an immune-mediated disease that affects 1%–2% of the European and North American population. While topical agents such as corticosteroids and vitamin D derivatives are prescribed for mild disease, they are generally unable to adequately control patients with more severe disease. Over the past decade, research into the immunopathogenesis of psoriasis, including investigations into the role of tumor necrosis factor-alpha and more recently interleukins (IL) 12/23, has led to the advent of targeted biologic therapies based on the central role of a new subset of T cells, Th17. Because of their increased specificity, biologic agents have revolutionized short- to medium-term treatment outcomes and safety profiles for moderate to severe disease over previously gold standard systemic agents. The immunopathogenesis of the disease is still a focus for researchers and novel targets for future agents are being discovered and investigated in clinical trials. In particular, specifically targeting the IL-23/Th17 pathway has given rise to IL-23p19 and IL-17 antagonists, both of which have shown significant promise in clinical trials. IL-22 is involved in keratinocyte proliferation and is being studied as a treatment target for psoriasis. New small molecule oral agents, including Janus kinase and phosphodiesterase inhibitors are currently in phase 2 and 3 clinical trials

Calculating the virtual cohomological dimension of the automorphism group of a RAAG

We describe an algorithm to find the virtual cohomological dimension of the automorphism group of a right-angled Artin group. The algorithm works in the relative setting; in particular it also applies to untwisted automorphism groups and basis-conjugating automorphism groups. The main new tool is the construction of free abelian subgroups of certain Fouxe-Rabinovitch groups of rank equal to their virtual cohomological dimension, generalizing a result of Meucci in the setting of free groups.Comment: 15 pages, 2 figures. Revised background on RORGs, small changes elsewhere. Accepted to appear in Bulletin of the LM

Fourth-Generation Fan Assessment Numeration System (FANS) Design and Performance Specifications

The Fan Assessment Numeration System (FANS) is a measurement device for generating ventilation fan performance curves. Three different-sized FANS currently exist for assessing ventilation fans commonly used in poultry and livestock housing systems. All FANS consist of an array of anemometers inside an aluminum shroud that traverse the inlet or outlet of a ventilation fan. The FANS design has been updated several times since its inception and is currently in its fourth-generation (G4). The current design iteration (FANS-G4) is reported in this article with an emphasis on the hardware and software control, data acquisition systems, and operational reliability. Six FANS-G4 units were fabricated at the University of Kentucky (UK) Agricultural Machinery Research Laboratory and calibrated at the University of Illinois Urbana-Champaign (UIUC) Bioenvironmental and Structural Systems (BESS) Laboratory. Results demonstrated that the FANS-G4 was capable of measuring volumetric airflow to within 0.6% of full-scale (FS), which ranged from 15,000 to 56,000 m3 h-1

Biofilter Media Characterization Using Water Sorption Isotherms

Compost material has been used extensively as a gas‐phase biofilter media for contaminant gas treatment in recent years. One of the biggest challenges in the use of this type of material is adequate control of compost moisture content and understanding its effect on the biofiltration process. The present work provides a methodology for characterization of biofilter media under low moisture conditions. Results indicated that low levels of equilibrium moisture content (EMC) were obtained for high levels of equilibrium relative humidity (ERH), i.e., 99% ERH produced EMC of approximately 20% (dry basis) at 25° C. Most bacteria struggle to survive in environments with ERH levels lower than 95%. Compost material from the same source was sieved into four compost particle size (PS) ranges to evaluate its water sorption behavior: 4.76 mm \u3e PS1 \u3e 3.36 mm \u3e PS2 \u3e 2.38 mm \u3e PS3 \u3e 2.00 mm \u3e PS4 \u3e 1.68 mm. Observed data were tested against isotherm models for their goodness‐of‐fit. Seven isotherm models were compared: (1) Langmuir; (2) Freundlich; (3) Sips; (4) Brunauer, Emmett, and Teller (BET); (5) BET for n‐layers; (6) Guggenheim, Anderson, de Boer (GAB); and (7) Henderson. In comparison with the other models, the Henderson model provided the best fit, as determined by the best combination of regression coefficient standard errors (Δ) and coefficients of determination (r2) for all four particle size ranges tested (95% confidence interval, C.I., and prediction interval, P.I.). The Henderson model was then used to test for significant differences in isotherms by particle size ranges.The four tested particle size ranges were not significantly different from each other (p \u3c 0.05), indicating similar water sorption behavior. Data from all four particle size ranges were pooled and regressed, and the minimum required moisture to maintain ERH at or above 95% was 16.41% ± 2.68% (dry basis)

Why do drivers become safer over the first three months of driving? A longitudinal qualitative study

Drivers are at high crash risk when they begin independent driving, with liability decreasing steeply over the first three months. Their behavioural development, and other changes underlying improved safety are not well understood. We adopted an innovative longitudinal qualitative design, with thirteen newly qualified drivers completing a total of 36 semi-structured interviews, one, two and three months after acquiring a full UK driving license. The interviews probed high-risk factors for new drivers, as well as allowing space for generating novel road safety issues. Analysis adopted a dual deductive and inductive interpretative thematic approach, identifying three super-ordinate themes: (1) Improvements in car control skills and situation awareness; (2) A reduction in the thrill of taking risks when driving against a background of generally increasing driving speed; (3) Early concerns about their social status in the eyes of other road users during the early stages of driving, which may put pressure on them to drive faster than they felt comfortable with. The study provides important new leads towards understanding how novice driving becomes safer over the first few months of driving, including how well-studied concepts of driving skill and style may change during development of independent driving, and a focus on the less rigorously studied concept of social status

Development of a microwave calorimeter for simultaneous thermal analysis,

An instrument has been developed for monitoring cure processes under microwave heating conditions. The main function of the instrument was a calorimeter for performing microwave thermal analysis. A single model resonant cavity was used as the heating cell in the microwave calorimeter. Thermal analysis measurements were obtained by monitoring the variation in the microwave power that was required to maintain controlled heating of the sample. The microwave thermal analysis data were analogous to conventional differential scanning calorimetry measurements. The dielectric properties of the sample, as a function of the extent of cure, have been obtained using perturbation theory from the changes in resonant frequency and quality factor of the microwave cavity during heating. Additionally, remote sensing fibre-optic probes have been employed to measure real time in situ infrared spectra of the sample during the cure reaction. In this paper, we describe the design and operation of the microwave calorimeter. Examples of experimental results are also presented

Characterizing Physical Properties of Gas-Phase Biofilter Media

Gas-phase biofiltration is an effective technology for reduction of odors and trace-gas contaminants. Significant contributions to the technical literature regarding the characterization of biofilter media have been generated in the past two decades. Nevertheless, the information produced has not been systematically organized. The objective of this study is to demonstrate and document methods for physical characterization of gas-phase compost biofilters (GPCB). The inclusion of moisture content, compaction, and particle size effects in the determination of media bulk density and porosity, field capacity, drying rate analysis, water sorption isotherms, and resistance to airflow is demonstrated. Results indicated that: (1) higher moisture content led to about 2% reduction in porosity after compaction; (2) biofilter media sieved into three particle size ranges (12.5 mm \u3e PSR1 \u3e 8.0 mm \u3e PSR2 \u3e 4.75 mm \u3e PSR3 \u3e 1.35 mm) produced significantly different media field capacities, i.e., 52.8% (PSR1), 61.6% (PSR2), and 72.2% (PSR3) on a wet basis; (3) a drying rate analysis provides important information regarding media-water relations and can be potentially used for in situ indirect media moisture monitoring (as shown in previous work, changes in drying rate significantly affected ammonia removal and nitrous oxide generation); (4) the Henderson isotherm can be accurately used for dry organic media to determine the minimum moisture required for microbial activity; and finally (5) the combination of high airflow and high moisture content drastically increased pressure drop up to 65-fold (6350 Pa m-1) compared to the lowest pressure drop (98 Pa m-1). Further, the research community should integrate efforts to elaborate standard methods and protocols for physical characterization of gas-phase biofilter media before and during biofilter operation

Treatment algorithm for infants diagnosed with spinal muscular atrophy through newborn screening

Spinal muscular atrophy (SMA) is an autosomal recessive disease characterized by the degeneration of alpha motor neurons in the spinal cord, leading to muscular atrophy. SMA is caused by deletions or mutations in the survival motor neuron 1 gene (SMN1). In humans, a nearly identical copy gene, SMN2, is present. Because SMN2 has been shown to decrease disease severity in a dose-dependent manner, SMN2 copy number is predictive of disease severity. To develop a treatment algorithm for SMA-positive infants identified through newborn screening based upon SMN2 copy number. A working group comprised of 15 SMA experts participated in a modified Delphi process, moderated by a neutral third-party expert, to develop treatment guidelines. The overarching recommendation is that all infants with two or three copies of SMN2 should receive immediate treatment (n = 13). For those infants in which immediate treatment is not recommended, guidelines were developed that outline the timing and appropriate screens and tests to be used to determine the timing of treatment initiation. The identification SMA affected infants via newborn screening presents an unprecedented opportunity for achievement of maximal therapeutic benefit through the administration of treatment pre-symptomatically. The recommendations provided here are intended to help formulate treatment guidelines for infants who test positive during the newborn screening process